This purpose of this study to identify brain mechanisms mediating the symptoms of bipolar disorder in children and adolescents. Approximately 80 patients and matched controls have been assessed on a battery of such paradigms. Taken together, these data indicate that children with BPD have difficulty adapting their behavior in response to changes in emotional stimuli in their environment. These deficits are evident on response reversal tasks, a task testing their ability to inhibit a dominant motor response and initiate another, and a task that assesses their behavior in the context of frustration. In addition, our data indicate that children with BPD have difficulty identifying facial emotion accurately. Using functional MRI, we have identified amygdala hyperactivity that is associated with the face labeling deficit, and prefrontal and striatal abnormalities associated with deficits in motor inhibition and response flexibility. Based on these findings, we are initiating genetic studies aimed at identifying associations between polymorphisms associated with bipolar disorder and abnormal patterns of brain activation identified with functional MRI. In addition, we have begun a study of children who are at risk for BPD because they have a parent or sibling with the illness. The goal of this study is to ascertain whether the behavioral deifcits that we identified are familial and therefore may be candidate endophenotypes for BPD. In addition, this year we began recruiting children with ADHD as a psychiatric comparison group for children with BPD. Finally, we continue to assess the psychiatric status of family members, bank genetic samples from patients and parents for use in future studies, and follow the patients longitudinally (clinically and with structural MRI scans).